Modulation of voltage- and ligand-gated ion channels by neuronal P2Y receptors

Kerstin Wirkner, L. Köles, S. Fürst, Peter Illes

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The present review summarizes data about the properties, distribution, and effects of neuronal P2Y receptors. Extracellular nucleotide receptors can be classified into two types belonging either to the P2X (ligand-gated cationic channels) or the P2Y type (G protein-coupled receptors). Neuronal P2Y receptors comprise five cloned and functionally defined classes of which P2Y1, P2Y6, P2Y11, P2Y12, and P2Y13 occur in the central nervous system. Various types of P2Y receptors stimulate inwardly rectifying potassium channels, positively or negatively modulate the high-voltage activated Ca2+ current and increase the intracellular free Ca2+ concentration in neuronal preparations. Moreover, in a subpopulation of pyramidal cells of the rat prefrontal cortex (PFC), the P2Y2 receptor potentiates the function of a ligand-gated cationic channel, the N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. This effect is G protein-mediated and utilizes the phospholipase C/inositol 1,4,5-trisphosphate/ Ca2+/calmodulin kinase II pathway. It appears that P2Y2 receptors situated at astrocytes release glutamate, which in turn modulates NMDA receptors of neighbouring neurons via stimulation of group I metabotropic glutamate receptors. In contrast, P2Y1 receptors inhibit the conductance of NMDA receptor-channels in all PFC pyramidal cells investigated. This effect is fast in onset and does not depend on G protein activation. It is suggested that P2Y1 receptors alter the function of NMDA receptors by a direct protein-protein coupling in the membrane. Because ATP and dopamine are supposed to be coreleased from dopaminergic fibers onto layer V pyramidal cells, both neurotransmitters may interact with the neuronal NMDA receptor. Hence, D1 dopamine receptors and P2Y1/P2Y2 receptors may be involved in the fine tuning of higher order cognitive functions including learning and memory.

Original languageEnglish
Pages (from-to)49-55
Number of pages7
JournalDrug Development Research
Volume59
Issue number1
DOIs
Publication statusPublished - May 1 2003

Fingerprint

Ligand-Gated Ion Channels
Purinergic P2Y2 Receptors
Purinergic P2Y1 Receptors
N-Methyl-D-Aspartate Receptors
Pyramidal Cells
Modulation
Electric potential
Prefrontal Cortex
GTP-Binding Proteins
Inwardly Rectifying Potassium Channel
Ligands
Dopamine D1 Receptors
Calcium-Calmodulin-Dependent Protein Kinases
Metabotropic Glutamate Receptors
Inositol 1,4,5-Trisphosphate
Glutamate Receptors
Neurology
Type C Phospholipases
N-Methylaspartate
G-Protein-Coupled Receptors

Keywords

  • Cortical pyramidal neurons
  • NMDA receptors
  • P2 purinoceptors

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Modulation of voltage- and ligand-gated ion channels by neuronal P2Y receptors. / Wirkner, Kerstin; Köles, L.; Fürst, S.; Illes, Peter.

In: Drug Development Research, Vol. 59, No. 1, 01.05.2003, p. 49-55.

Research output: Contribution to journalArticle

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